Relationship between Parathyroid Hormone Levels and Hazards of Fracture, Vascular Events and Death in Stage 3 and 4 Chronic Kidney Disease

Abstract

word count: 295Manuscript word count: 2475 of 3500 max Abstract (300 words, limit =300) Background and Objectives: Chronic kidney disease (CKD) affects ~20% of older adults and secondary hyperparathyroidism (HPT) is a common condition in these patients. Studies have linked HPT to a greater risk of fractures, vascular events and mortality. However, the optimal parathyroid hormone (PTH) level needed to minimize these events remains uncertain. Design, setting, participants and measurements:We assessed relationships between baseline serum PTH levels and the subsequent 10-year probability of clinical fractures, vascular events and death in stage 3 and 4 CKD patients. We used Marshfield Clinic Health System electronic health records to analyze data from adult CKD patients spanning from 1985 to 2013. We required ≥ 2 PTH measurements at baseline and used ICD-9 codes to identify medical conditions, fractures, vascular events and death. In multivariate models, we assessed relationships between serum PTH and the three clinical outcomes, controlling for age, gender, co-morbidities and osteoporosis medication.Results: 7594 subjects had a mean age of 68±13 years and 55% were women. Fractures, vascular events and death occurred in 19%, 60% and 29% of the cohort, respectively. In multivariate models including the whole cohort regardless of PTH assay, the probability of fracture, vascular events and death were minimized at a PTH of 23, 50 and 50 pg/mL. Below these cutpoints, the probability of fractures and death dramatically increased. When confining the analysis to patients measured using a 2 nd generation PTH assay (n=5108), the hazards of fracture, vascular events and death were minimized at a PTH of zero, 60 and 58 pg/mL. Any of these clinical outcomes was minimized at a baseline PTH of 58 pg/mL. Conclusions:Our study suggests that parathyroid hormone levels around 60 pg/mL might reduce the risk of fractures, vascular events and death in CKD patients. Additional epidemiologic studies and randomized clinical trials are needed to confirm these findings.PTH target that would minimize these adverse outcomes, thus guiding the design of randomized controlled clinical trials. Given the limitations of our study, it is important to verify these findings in another database. If we can confirm a proposed target PTH level at which fractures, vascular events and death are reduced, then randomized clinical trials will be needed to verify that treatment of HPT improves the health of CKD patients. Disclosures: none